What is an example of an infusion related reaction?: Cytokine Release Syndrome Explained

October 12, 2025 •

4 min read

Infusion-related reactions (IRRs) are adverse events that can occur during or within 24 hours of a drug infusion. A common and important example of an infusion related reaction is cytokine release syndrome (CRS), a systemic inflammatory response triggered by immune system activation.

Quick Summary

Infusion reactions are adverse events linked to intravenous drug administration, which can include hypersensitivity reactions like anaphylaxis or non-allergic responses like cytokine release syndrome (CRS). Symptoms range from mild (fever, chills) to severe (hypotension, respiratory distress), requiring immediate monitoring and appropriate management based on severity and underlying mechanism.

Key Points

Cytokine Release Syndrome (CRS) is a Non-Allergic Reaction: An example of an infusion related reaction is CRS, a systemic inflammatory response caused by the widespread activation of immune cells and subsequent release of cytokines, not by a classic allergic mechanism.
Anaphylaxis is an Allergic Infusion Reaction: A severe, potentially life-threatening immune-mediated reaction known as anaphylaxis is another key example of an infusion reaction, often triggered by IgE antibodies.
Monoclonal Antibodies and Platinum Agents are High-Risk: Drugs like the monoclonal antibody Rituximab are frequently associated with CRS, while platinum-based chemotherapies like carboplatin are known for causing hypersensitivity reactions, especially in later cycles.
Premedication and Infusion Rates Mitigate Risk: Strategies such as using corticosteroids and antihistamines as premedication and administering infusions at a slower rate are crucial for preventing or reducing the severity of infusion reactions.
Immediate Response is Critical: If an infusion reaction occurs, the infusion must be stopped immediately. Treatment varies based on the reaction type and severity, ranging from supportive care to epinephrine for severe anaphylaxis.
Differentiation Guides Treatment: Distinguishing between CRS and anaphylaxis is critical, as their mechanisms differ. Anaphylaxis, being a true allergy, may require permanent cessation of the drug, whereas CRS may allow for future infusions with more aggressive premedication.

Understanding Infusion Related Reactions

An infusion-related reaction (IRR) is any adverse event that occurs during or shortly after the administration of a drug via infusion. These reactions are not always true allergies; they can be categorized based on their underlying mechanisms. The two primary categories are immune-mediated (true allergic reactions) and non-immune-mediated (non-allergic or pseudo-allergic) reactions. The distinction is crucial for proper diagnosis, management, and deciding on future treatments. Most reactions are mild and transient, but some can be severe and life-threatening, such as anaphylaxis. Healthcare providers use the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) to grade the severity of IRRs, which guides their response and informs decisions on continuing therapy.

What is an example of an infusion related reaction? Cytokine Release Syndrome

One of the most significant and well-documented examples of an infusion related reaction is Cytokine Release Syndrome (CRS). This is a non-immune-mediated inflammatory response that occurs when a drug, often a monoclonal antibody or another immunotherapy, activates immune cells on a large scale. These activated immune cells then release a massive amount of inflammatory signaling proteins called cytokines into the bloodstream.

Commonly associated drugs

Monoclonal Antibodies: Rituximab, a monoclonal antibody used in lymphoma and other conditions, is well known for causing CRS, particularly during the first infusion.
CAR T-Cell Therapy: This advanced form of immunotherapy can also trigger CRS as engineered T-cells multiply and attack target cells, releasing cytokines.

Typical Symptoms and Onset CRS often presents as a flu-like illness within minutes to hours of the infusion. Key symptoms include:

High fever and chills
Headache and fatigue
Nausea, vomiting, and diarrhea
Muscle and joint pain
Tachycardia and hypotension (low blood pressure)
Rash
Difficulty breathing

In severe cases, CRS can lead to life-threatening complications such as respiratory distress, multi-organ system failure, and shock. Fortunately, most CRS cases are mild to moderate and manageable by stopping or slowing the infusion rate and providing supportive care.

Another example: Anaphylaxis

Anaphylaxis is a severe, rapid, and life-threatening immune-mediated reaction that can also be considered an infusion reaction. It involves an IgE antibody-mediated response, leading to a systemic allergic reaction. Anaphylaxis can occur with many different drugs, including some chemotherapies.

Commonly associated drugs

Platinum Compounds: While not always IgE-mediated, platinum-based chemotherapies like carboplatin and oxaliplatin are notorious for causing hypersensitivity reactions, with the risk increasing after several cycles of therapy.
Other Agents: Taxanes (like paclitaxel) and intravenous iron formulations can also cause allergic reactions, though pre-medication can help manage the risk.

Symptoms Anaphylaxis involves a rapid onset of severe symptoms, including:

Widespread hives and itching
Flushing of the face and neck
Swelling of the lips, tongue, and throat (angioedema)
Wheezing, shortness of breath, and respiratory distress
Severe hypotension and cardiovascular collapse

Management and Prevention Strategies

Prevention Strategies

Premedication: Many patients at risk for IRRs are given premedication with corticosteroids, antihistamines, and/or antipyretics before an infusion. This is a common practice for drugs like Rituximab and can significantly reduce the risk and severity of reactions.
Graduated Infusion Rates: Infusions, especially the first dose of a drug with a high risk of IRR, may be started at a slow rate and gradually increased. This allows the medical team to monitor for early signs of a reaction and stop the infusion if necessary.

Immediate Management If an IRR is suspected, the first action is to stop the infusion immediately and activate emergency procedures if needed. The specific treatment depends on the severity and type of reaction:

For mild symptoms: The infusion may be paused, and the patient given supportive care. Once symptoms resolve, the infusion may be restarted at a slower rate.
For moderate to severe reactions: Treatment may involve medications like epinephrine (for anaphylaxis), additional antihistamines, and corticosteroids.

Comparison of Cytokine Release Syndrome and Anaphylaxis


Feature	Cytokine Release Syndrome (CRS)	Anaphylaxis (True Allergy)
Mechanism	Non-immune mediated; large-scale release of inflammatory cytokines from activated immune cells.	IgE antibody-mediated immune response.
Timing	Often occurs during or shortly after the first infusion. Can be rapid in onset.	Can occur immediately or after a delayed period. Risk often increases with subsequent exposures (especially with platinum agents).
Typical Drugs	Monoclonal antibodies (e.g., Rituximab), CAR T-cell therapy.	Platinum compounds (e.g., Carboplatin), taxanes, IV iron, some contrast dyes.
Common Symptoms	Fever, chills, headache, fatigue, myalgia, nausea, hypotension, tachycardia.	Hives, itching, flushing, angioedema, wheezing, hypotension, shock.
Onset Risk	Highest risk typically with the first infusion.	Can occur at any exposure, but risk may be cumulative with repeat doses for some drugs.
Management Focus	Management of systemic inflammation, often with supportive care. May involve corticosteroids.	Stopping the reaction with epinephrine and supportive measures. Subsequent doses may require desensitization protocols.

Risk Factors and Incidence

Patient-specific factors can increase the likelihood of experiencing an IRR. These include prior history of infusion reactions, a high disease burden, and the type of drug being administered. Certain drug classes have a higher reported incidence of IRRs:

Monoclonal Antibodies: Can have high rates, especially during the initial infusions. For example, Rituximab's initial infusion can have a reaction rate of over 70%, though this decreases in later doses.
Taxanes (Paclitaxel, Docetaxel): Early-cycle reactions are relatively common, often occurring within minutes.
Platinum Agents (Carboplatin, Oxaliplatin): Reactions typically occur after multiple cycles, often the sixth or later.

Conclusion

An infusion related reaction is a potential complication of intravenous drug therapy, with cytokine release syndrome (CRS) and anaphylaxis being two prominent examples. While CRS is a non-immune inflammatory response often seen with immunotherapies like monoclonal antibodies, anaphylaxis is a severe, true allergic reaction. Understanding the different mechanisms, symptoms, and associated drugs is vital for healthcare professionals to effectively manage these events. Most reactions can be prevented or mitigated with proper premedication and monitoring, ensuring patient safety during and after infusion therapy. For more detailed information, consult authoritative healthcare resources such as this protocol summary for management of infusion-related reactions from BC Cancer.

Frequently Asked Questions

Common symptoms can range from mild, such as fever, chills, headache, flushing, and rash, to more severe signs like hypotension (low blood pressure), breathing difficulties, wheezing, and swelling of the face and throat.

Treatment varies by severity. Mild reactions may only require pausing or slowing the infusion. Moderate to severe reactions often require additional medication, such as antihistamines, corticosteroids, or epinephrine, and ongoing patient monitoring.

An allergic reaction (like anaphylaxis) is an immune-mediated response involving antibodies. A non-allergic or pseudo-allergic reaction (like Cytokine Release Syndrome) does not involve antibodies and is caused by the non-immune-related release of inflammatory mediators.

While not always preventable, the risk and severity can be minimized through strategies like premedication (e.g., with antihistamines and steroids), adjusting the infusion rate, and closely monitoring the patient during the infusion.

Some of the drugs most commonly associated with infusion reactions include monoclonal antibodies (e.g., Rituximab), platinum-based chemotherapies (e.g., Carboplatin), taxanes (e.g., Paclitaxel), and intravenous iron products.

The timing can vary. Many infusion reactions, especially non-allergic ones like CRS, happen during the first few minutes or hours of an infusion. However, some allergic reactions, like those to platinum agents, may occur after multiple treatment cycles.

The infusion should be stopped immediately. The healthcare team should be notified, and vital signs should be monitored to assess the patient's condition. Emergency procedures should be activated if the reaction is severe.